A Phase II, Single-Center, Randomized, Blinded, Controlled Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacodynamics of a Recombinant Human Anti-Rabies Virus Monoclonal Antibody Injection in Healthy Subjects
Primary Objective of the study: （1）To evaluate the safety, tolerability, and Rabies Virus Neutralizing Activity (RVNA) of different doses of a recombinant human anti-rabies virus monoclonal antibody injection (referred to as the anti-rabies mAb), administered alone or in combination with a human rabies vaccine, compared to human rabies immune globulin, in healthy adult participants aged 18-60. Secondary Objective of the study: 1. To evaluate the pharmacokinetics (PK) of the anti-rabies mAb administered alone or in combination with a human rabies vaccine in healthy adult participants aged 18-60. 2. To evaluate the incidence of anti-drug antibodies for the anti-rabies mAb compared to human rabies immune globulin, administered alone or in combination with a human rabies vaccine, in healthy adult participants aged 18-60. 3. To provide a basis for dose selection for Phase III clinical studies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
200
On Day 0, administer via intramuscular injection into the lateral thigh. It is strictly prohibited to use the same syringe as the rabies vaccine or to co-administer at the same injection site.
On Day 0, administration shall be performed via intramuscular injection into the lateral aspect of the thigh. It is strictly prohibited to use the same syringe as the rabies vaccine or to administer both agents at the same injection site.
On Day 0, administration shall be performed via intramuscular injection into the lateral aspect of the thigh. It is strictly prohibited to use the same syringe as the rabies vaccine or to administer both agents at the same injection site.
Lanzhou Institute of Biological Products Co., Ltd.
Lanzhou, Gansu, China
Occurrence of any local and systemic adverse events (AEs) within at least 30 minutes after administration of the investigational product/vaccine.
Local and systemic adverse events (AEs)
Time frame: At least 30 minutes after administration
Occurrence of any local AEs, systemic AEs, and serious adverse events (SAEs) from the administration of the investigational product on Day 0 until the last visit.
Local AEs, systemic AEs, and serious adverse events (SAEs)
Time frame: 0-105 days
Vital signs changes from baseline at different observation time points following the administration of the investigational product/vaccine.
Tympanic temperature（℃）
Time frame: 0-105 Days
Vital signs changes from baseline at different observation time points following the administration of the investigational product/vaccine.
Systolic Pressure and Diastolic Pressure (Sitting Position) （mmHg）
Time frame: 0-105 Days
Vital signs changes from baseline at different observation time points following the administration of the investigational product/vaccine.
Pulse（bpm）
Time frame: 0-105 Days
Changes in 12-lead electrocardiogram findings from baseline at different observation time points following administration of the investigational product/vaccine.
12-lead electrocardiogram（Heart Rate，bpm）
Time frame: 0-105 Days
Changes in 12-lead electrocardiogram findings from baseline at different observation time points following administration of the investigational product/vaccine.
12-lead electrocardiogram（ Heart Rhythm）
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On Days 0, 3, 7, 14, and 28, administer via intramuscular injection into the deltoid muscle of the upper arm. Injection into the gluteal region is prohibited. The injection on Day 0 should be administered as soon as possible after the administration of the investigational product.
Time frame: 0-105 Days
Changes in 12-lead electrocardiogram findings from baseline at different observation time points following administration of the investigational product/vaccine.
12-lead electrocardiogram（ST Segment，mV）
Time frame: 0-105 Days
Changes in 12-lead electrocardiogram findings from baseline at different observation time points following administration of the investigational product/vaccine.
12-lead electrocardiogram（Abnormal Q Wave，ms）
Time frame: 0-105 Days
Changes in chest X-ray findings from baseline at different observation time points following administration of the investigational product/vaccine.
Chest X-ray（Cardiothoracic Ratio，\>0.5）
Time frame: 0-105 Days
Changes in chest X-ray findings from baseline at different observation time points following administration of the investigational product/vaccine.
Chest X-ray（Pulmonary Nodule Size，mm）
Time frame: 0-105 Days
Changes in chest X-ray findings from baseline at different observation time points following administration of the investigational product/vaccine.
Chest X-ray（Costophrenic Angle，cm）
Time frame: 0-105 Days
Changes in chest X-ray findings from baseline at different observation time points following administration of the investigational product/vaccine.
Chest X-ray（Tracheal Position，cm）
Time frame: 0-105 Days
Changes in complete blood count (CBC) results from baseline at different observation time points following administration of the investigational product/vaccine.
White Blood Cell Count（×10⁹/L）
Time frame: 0-105 Days
Changes in complete blood count (CBC) results from baseline at different observation time points following administration of the investigational product/vaccine.
Hemoglobin（g/L）
Time frame: 0-105 Days
Changes in complete blood count (CBC) results from baseline at different observation time points following administration of the investigational product/vaccine.
Platelet Count（×10⁹/L）
Time frame: 0-105 Days
Changes in complete blood count (CBC) results from baseline at different observation time points following administration of the investigational product/vaccine.
Neutrophil Percentage（%）
Time frame: 0-105 Days
Changes in urinalysis results from baseline at different observation time points following administration of the investigational product/vaccine.
Protein（g/L）
Time frame: 0-105 Days
Changes in urinalysis results from baseline at different observation time points following administration of the investigational product/vaccine.
Glucose（mmol/L）
Time frame: 0-105 Days
Changes in urinalysis results from baseline at different observation time points following administration of the investigational product/vaccine.
White Blood Cells in Urine（/μL）
Time frame: 0-105 Days
Changes in urinalysis results from baseline at different observation time points following administration of the investigational product/vaccine.
Urine Erythrocytes （/μL）
Time frame: 0-105 Days
Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine.
Blood Glucose （mmol/L）
Time frame: 0-105 Days
Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine.
Potassium （mmol/L）
Time frame: 0-105 Days
Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine.
Creatinine （µmol/L）
Time frame: 0-105 Days
Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine.
Alanine Aminotransferase（U/L）
Time frame: 0-105 Days
Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine.
Sodium（mmol/L）
Time frame: 0-105 Days
Changes in blood biochemistry results from baseline at different observation time points following administration of the investigational product/vaccine.
estimated Glomerular Filtration Rate（mL/min/1.73m²）
Time frame: 0-105 Days
Changes in routine coagulation test results from baseline at different observation time points following administration of the investigational product/vaccine.
Prothrombin Time（s）
Time frame: 0-105 days
Pharmacodynamic Endpoints
The positive rate (with a positivity threshold of RVNA ≥ 0.5 IU/mL) of serum rabies virus neutralizing antibodies (RVNA) were measured at the following time points: within 1 hour before the administration of the investigational product on Day 0, and at 4 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine.
Time frame: 0-105 Days
Pharmacodynamic Endpoints
The geometric mean concentration (GMC) of serum rabies virus neutralizing antibodies (RVNA) were measured at the following time points: within 1 hour before the administration of the investigational product on Day 0, and at 4 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine.
Time frame: 0-105 Days
Pharmacokinetic Endpoints
The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. The following pharmacokinetic (PK) endpoints were calculated: Cmax.
Time frame: 105 Days
Pharmacokinetic Endpoints
The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. The following pharmacokinetic (PK) endpoints were calculated: AUC0-t.
Time frame: 105 Days
Pharmacokinetic Endpoints
The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. The following pharmacokinetic (PK) endpoints were calculated: AUC0-∞.
Time frame: 105 Days
Pharmacokinetic Endpoints
The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. The following pharmacokinetic (PK) endpoints were calculated: Tmax.
Time frame: 105 Days
Pharmacokinetic Endpoints
The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. The following pharmacokinetic (PK) endpoints were calculated: t1/2.
Time frame: 105 Days
Pharmacokinetic Endpoints
The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. The following pharmacokinetic (PK) endpoints were calculated: Vd/F.
Time frame: 105 Days
Pharmacokinetic Endpoints
The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. The following pharmacokinetic (PK) endpoints were calculated: Kel.
Time frame: 105 Days
Pharmacokinetic Endpoints
The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. The following pharmacokinetic (PK) endpoints were calculated: MRT.
Time frame: 105 Days
Pharmacokinetic Endpoints
The concentrations of LZR08 and LZR07 antibodies in serum were measured within 1 hour before the administration of the investigational product on Day 0 and at 12 hours, 1 day, 2 days, 3 days, 5 days, 7 days, 10 days, 14 days, 28 days, 42 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. The following pharmacokinetic (PK) endpoints were calculated: CL/F.
Time frame: 105 Days
Anti-drug Antibodies (ADA)
The positive rate of serum anti-drug antibodies (ADA) against LZR08/LZR07 were assessed within 1 hour before the administration of the investigational product on Day 0 and at 7 days, 28 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. For trial participants who tested positive for ADA, further evaluation was conducted to determine whether these were neutralizing antibodies against LZR08/LZR07.
Time frame: 105 Days
Anti-drug Antibodies (ADA)
The titer of serum anti-drug antibodies (ADA) against LZR08/LZR07 were assessed within 1 hour before the administration of the investigational product on Day 0 and at 7 days, 28 days, 56 days, 84 days, and 105 days after the administration of the investigational product/vaccine. For trial participants who tested positive for ADA, further evaluation was conducted to determine whether these were neutralizing antibodies against LZR08/LZR07.
Time frame: 105 Days